Date: July 2019

Rhabdoid tumours are highly aggressive childhood cancers that are fatal in most children, often within a year of diagnosis. These cancers carry mutations in SMARCB1, a gene involved in regulating the function of other genes. Current treatment for rhabdoid tumours cures very few children and often results in life-changing side-effects in survivors. Little is understood as to why treatment is effective in some children whilst not in others, or why the effect of initially beneficial treatment quickly wears off. There is an urgent need to discover new treatments with greater effectiveness as well as design molecular tests that can identify which children will benefit from existing drugs.

This project is aimed at indentifying which are the cellular molecules that drive growth and spread of rhabdoid tumours, and to use this information to nominate new treatment strategies and develop real-time diagnostic tests for personalising treatment in patients. This study will use tissue samples obtained from rhabdoid tumour patients as well as from a group of closely related paediatric and adolescent cancers which similarly have SMARCB1 mutations.

By conducting comprehensive molecular profiling of these patient specimens, we will curate the protein-specific molecular drivers in this tumour type and link this information to known drug candidates and develop ways to predict for therapy response. In addition to the identification of new drug targets, we expect that our research will provide a means of estimating the sensitivity of an individual patient's cancer to available drugs ahead of starting treatment, enabling the development of a personalised approach to treating rhabdoid tumours.

Going forward, our work will provide the basis for new anticancer drug trials in rhabdoid tumours (and other SMARCB1 mutant cancers) that aim to establish effective and safe new treatments for these devastating diseases.